The serum and glucocorticoid inducible protein kinase(SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase(PI3K) signallin...The serum and glucocorticoid inducible protein kinase(SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase(PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. This perspective intends to give an overview on the involvement of SGKs(particularly SGK3) in cancer progression, and compares the actions of SGK3 and AKT in cell cycle regulation, oncogenic signalling, and the potential as a therapeutic target for cancer.展开更多
目的:观察熟地有效成分甘露三糖对高浓度皮质酮诱导海马神经元损伤及学习记忆相关信号转导分子表达的影响。方法:用24小时新生大鼠原代培养海马神经细胞。第八天用药处理,将细胞分为5组:1:正常对照组;2:1×10-4M高浓度皮质酮模型组;...目的:观察熟地有效成分甘露三糖对高浓度皮质酮诱导海马神经元损伤及学习记忆相关信号转导分子表达的影响。方法:用24小时新生大鼠原代培养海马神经细胞。第八天用药处理,将细胞分为5组:1:正常对照组;2:1×10-4M高浓度皮质酮模型组;3:10-4 M CORT+3nM RU38486拮抗剂组;4:10-4 M CORT+0.1g/L甘露三糖组;5:10-4 M CORT+40uM多奈哌齐阳性对照组。24h后,通过SYTO13-PI双荧光染色观察各组细胞的形态及存活情况,MTT法测定细胞活性,Western Blot检测学习记忆信号转导通路相关分子GCR、BDNF、SGK蛋白表达。结果:与正常组相比,模型组细胞死亡较多,细胞活力下降,GCR、BDNF、SGK蛋白表达均显著性降低;如上改变又均被皮质酮受体拮抗剂RU38486逆转;甘露三糖(0.1g/L)同阳性对照多奈派齐(40μM)均明显减少死细胞数量,提高细胞活力,提高模型细胞GCR、BDNF、SGK蛋白表达。结论:熟地有效成分甘露三糖保护大鼠海马神经细胞免遭高浓度皮质酮的损伤,通过调节学习记忆信号转导途径中的重要蛋白GCR、BDNF、SGK表达从而改善高浓度皮质酮致学习记忆功能退化。展开更多
应激会对动物的学习记忆能力产生影响,这种影响呈一种倒U型关系,即当应激强度过大或时间过长时这种影响往往是一种损伤,而适度的应激会对学习记忆产生促进作用。目前认为应激激活了下丘脑-垂体-肾上腺(hypothalamo-pituitary-adrenal,H...应激会对动物的学习记忆能力产生影响,这种影响呈一种倒U型关系,即当应激强度过大或时间过长时这种影响往往是一种损伤,而适度的应激会对学习记忆产生促进作用。目前认为应激激活了下丘脑-垂体-肾上腺(hypothalamo-pituitary-adrenal,HPA)轴,诱导糖皮质激素的释放。适量的糖皮质激素会促进长时程增强(long-term potentiation,LTP)的形成,从而促进学习记忆。血清/糖皮质激素诱导激酶(serum and glucocorticoid regulated protein kinase,SGK)作为糖皮质激素诱导的一个激酶,参与了多种离子通道的调节,能够促进神经元的存活和轴突的再生。研究发现SGK的表达也会促进空间学习记忆能力。展开更多
血清和糖皮质激素调节蛋白激酶-1(protein kinase regulation of serum and glucocorticoid,SGK1)是一个与丝氨酸-苏氨酸蛋白激酶等第二信使具有极高同源性的蛋白激酶。它作为多种信号转导通路和细胞磷酸化的级联交汇点,参与离子通道调...血清和糖皮质激素调节蛋白激酶-1(protein kinase regulation of serum and glucocorticoid,SGK1)是一个与丝氨酸-苏氨酸蛋白激酶等第二信使具有极高同源性的蛋白激酶。它作为多种信号转导通路和细胞磷酸化的级联交汇点,参与离子通道调节、细胞增殖、存活的细胞转导。在糖尿病病人中,高糖诱导SGK1活化,SGK1使得上皮钠离子通道(Epithelial sodium channel,ENaC)的表达增加。近些年来各种研究发现ENaC表达于非上皮组织,且对糖尿病血管病变,尤其是糖尿病视网膜病变的发病将发挥一定的作用。ENaC通过肾素-血管紧张素-醛固酮系统(Renin-angiotensin-aldosterone system,RAAS系统)介导,血管内皮NO生成减少,血管功能障碍;NADPH氧化酶功能障碍,参与病理性血管的生成;在高血糖条件下SGK作用于下游转录调控因子核转录因子κB(Nuclear factorκB,NF-κB),使得其在细胞核中含量增加,上调凋亡基因的表达,周细胞的凋亡增加。展开更多
Thrombopioetin (TPO), the critical regulator of platelet production, acts by binding to its cell surface receptor, c-Mpl. Yeast two-hybrid screening was performed to isolate the proteins interacting with the cytoplasm...Thrombopioetin (TPO), the critical regulator of platelet production, acts by binding to its cell surface receptor, c-Mpl. Yeast two-hybrid screening was performed to isolate the proteins interacting with the cytoplasmic domain of c-Mpl. 48 positive clones were isolated from 5 xxxxxxxxxx106 independent transformants. The results of sequence analysis demonstrate that they represent 13 different protein encoding sequences. Among them there are a partial coding sequence of serine/threonine protein kinase SGK (serum and glucocorticoid-inducible kinase ) and 14-3-3 theta protein partial coding sequence. GST-pull-down assay and co-im-munoprecipitation in mammal cells have confirmed the interaction between these two proteins and c-Mpl. By constructing a series of deleted c-Mpl cytoplasmic domain, the interaction region in c-Mpl cytoplasmic tail was localized in amino acids 523-554. At the same time, the directed interaction between SGK and 14-3-3 proteins also has been verified by yeast two-hybrid assay. The展开更多
A semi-gas kinetics (SGK) model for performance analyses of flowing chemical oxygen-iodine laser (COIL) is presented. In this model, the oxygen-iodine reaction gas flow is treated as a continuous medium, and the effec...A semi-gas kinetics (SGK) model for performance analyses of flowing chemical oxygen-iodine laser (COIL) is presented. In this model, the oxygen-iodine reaction gas flow is treated as a continuous medium, and the effect of thermal motions of particles of different laser energy levels on the performances of the COIL is included and the velocity distribution function equations are solved by using the double-parameter perturbational method. For a premixed flow, effects of different chemical reaction systems, different gain saturation models and temperature, pressure, yield of excited oxygen, iodine concentration and frequency-shift on the performances of the COIL are computed, and the calculated output power agrees well with the experimental data. The results indicate that the power extraction of the SGK model considering 21 reactions is close to those when only the reversible pumping reaction is considered, while different gain saturation models and adjustable parameters greatly affect the output power, the optimal threshold gain range, and the length of power extraction.展开更多
As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occur...As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.展开更多
基金supported by grants from the Ministry of Science and Technology of China (2014DFG32200)Shanghai Science and Technology Development Fund (15DZ2291600)the Thousand Talents Program in China ([2011]166)
文摘The serum and glucocorticoid inducible protein kinase(SGK) family members share similar structure, substrate specificity and function with AKT and signal downstream of the phosphatidylinositol 3-kinase(PI3K) signalling pathway. They regulate a range of fundamental cellular processes such as cell proliferation and survival, thereby playing an important role in cancer development. This perspective intends to give an overview on the involvement of SGKs(particularly SGK3) in cancer progression, and compares the actions of SGK3 and AKT in cell cycle regulation, oncogenic signalling, and the potential as a therapeutic target for cancer.
文摘地震数据去噪在地震资料处理中扮演着关键的角色,提升地震数据的信噪比将为后续高质量处理和精确解释奠定坚实基础。目前,地震数据去噪的方法已经得到了广泛发展,其中字典学习方法具有独特的优势。当前经典的K-奇异值分解(K-singular value decomposition,K-SVD)字典学习算法存在去噪结果损失了部分原始信号和计算效率不太理想等问题,为了将这些问题进一步优化,提出了一种基于顺序广义K-均值算法(sequential generalized K-means,SGK)的字典学习方法用于地震数据去噪。首先,从样本数据中提取随机位置的块,并移除空白块,以初始化字典。接着,在字典学习阶段,通过地震数据本身的特征自适应地构造出最新的稀疏表示字典。随后,利用学得的字典对包含噪声的地震数据分块进行去噪处理,将去噪后的块进行平均处理,并重新构建图像块,最终实现地震数据的去噪。通过合成数据和实际数据的实验,从信噪比、计算效率以及对有效信号的保护方面验证本文方法的去噪性能。
文摘目的:观察熟地有效成分甘露三糖对高浓度皮质酮诱导海马神经元损伤及学习记忆相关信号转导分子表达的影响。方法:用24小时新生大鼠原代培养海马神经细胞。第八天用药处理,将细胞分为5组:1:正常对照组;2:1×10-4M高浓度皮质酮模型组;3:10-4 M CORT+3nM RU38486拮抗剂组;4:10-4 M CORT+0.1g/L甘露三糖组;5:10-4 M CORT+40uM多奈哌齐阳性对照组。24h后,通过SYTO13-PI双荧光染色观察各组细胞的形态及存活情况,MTT法测定细胞活性,Western Blot检测学习记忆信号转导通路相关分子GCR、BDNF、SGK蛋白表达。结果:与正常组相比,模型组细胞死亡较多,细胞活力下降,GCR、BDNF、SGK蛋白表达均显著性降低;如上改变又均被皮质酮受体拮抗剂RU38486逆转;甘露三糖(0.1g/L)同阳性对照多奈派齐(40μM)均明显减少死细胞数量,提高细胞活力,提高模型细胞GCR、BDNF、SGK蛋白表达。结论:熟地有效成分甘露三糖保护大鼠海马神经细胞免遭高浓度皮质酮的损伤,通过调节学习记忆信号转导途径中的重要蛋白GCR、BDNF、SGK表达从而改善高浓度皮质酮致学习记忆功能退化。
文摘应激会对动物的学习记忆能力产生影响,这种影响呈一种倒U型关系,即当应激强度过大或时间过长时这种影响往往是一种损伤,而适度的应激会对学习记忆产生促进作用。目前认为应激激活了下丘脑-垂体-肾上腺(hypothalamo-pituitary-adrenal,HPA)轴,诱导糖皮质激素的释放。适量的糖皮质激素会促进长时程增强(long-term potentiation,LTP)的形成,从而促进学习记忆。血清/糖皮质激素诱导激酶(serum and glucocorticoid regulated protein kinase,SGK)作为糖皮质激素诱导的一个激酶,参与了多种离子通道的调节,能够促进神经元的存活和轴突的再生。研究发现SGK的表达也会促进空间学习记忆能力。
基金This work was supported by the Na-tional Natural Science Foundation of China (Grant No. 39670407).
文摘Thrombopioetin (TPO), the critical regulator of platelet production, acts by binding to its cell surface receptor, c-Mpl. Yeast two-hybrid screening was performed to isolate the proteins interacting with the cytoplasmic domain of c-Mpl. 48 positive clones were isolated from 5 xxxxxxxxxx106 independent transformants. The results of sequence analysis demonstrate that they represent 13 different protein encoding sequences. Among them there are a partial coding sequence of serine/threonine protein kinase SGK (serum and glucocorticoid-inducible kinase ) and 14-3-3 theta protein partial coding sequence. GST-pull-down assay and co-im-munoprecipitation in mammal cells have confirmed the interaction between these two proteins and c-Mpl. By constructing a series of deleted c-Mpl cytoplasmic domain, the interaction region in c-Mpl cytoplasmic tail was localized in amino acids 523-554. At the same time, the directed interaction between SGK and 14-3-3 proteins also has been verified by yeast two-hybrid assay. The
基金supported by the National Natural Science Foundation of China(Grant No.10032050).
文摘A semi-gas kinetics (SGK) model for performance analyses of flowing chemical oxygen-iodine laser (COIL) is presented. In this model, the oxygen-iodine reaction gas flow is treated as a continuous medium, and the effect of thermal motions of particles of different laser energy levels on the performances of the COIL is included and the velocity distribution function equations are solved by using the double-parameter perturbational method. For a premixed flow, effects of different chemical reaction systems, different gain saturation models and temperature, pressure, yield of excited oxygen, iodine concentration and frequency-shift on the performances of the COIL are computed, and the calculated output power agrees well with the experimental data. The results indicate that the power extraction of the SGK model considering 21 reactions is close to those when only the reversible pumping reaction is considered, while different gain saturation models and adjustable parameters greatly affect the output power, the optimal threshold gain range, and the length of power extraction.
文摘As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.
